Human immunodeficiency virus (HIV) is a RNA virus. The surface of this virus is a layer of double lipid membrane. The membrane encapsulates 2 single chain RNA and some important enzymes (e.g. reverse transcriptase, protease, integrase) and structural protein (p24, p17, p7, etc). The membrane surface of the virus has two very important glycoproteins gp120 and gp41. The gp120 is outside of the membrane, gp41 bestrides the double lipid membrane and forms a composite with gp120. Their main function is to recognize and attack cells having CD4 surface receptors in human immune system, such as lymphocyte (T cell), macrophage. HIV cannot be propagated in vitro, it can be replicated and regenerated only by means of human cells. The replication course of HIV can be approximately divided into following stages: binding and fusing of virus and host cells, reverse transcription of virus genes, integration, transcription and translation, and assembly and release of virus. HIV continuously replicates in such a circulation course, infects human immune cells, destroys human immune system, and finally causes the complete loss of human immune function, so that patients are placed in the risk of various infections without resistance ability. Theoretically, only if a drug can interrupt any link during the replication of virus, the purpose of inhibiting virus and treating diseases can be achieved.
Up to now, there are 30 kinds of chemical drugs and their combinations that have been approved to be marketed for clinic anti-HIV infection and treating AIDS. Existing drugs are divided into five classes in terms of action mechanism: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (Enfuvirtide), and entrance inhibitors (Maraviroc). The use of existing drugs alone or in combination can effectively inhibit the replication of virus, however, the main problem commonly faced is drug resistance. HIV viruses may exhibit some mutation after interacting with drugs. Mutated virus cannot be inhibited by drugs, and still continuously replicates a great deal of virus in vivo as before drug administration. Therefore, seeking and developing a new generation of anti-HIV drugs having new structure type, new action mechanism, new action target or exhibiting strong inhibition effect on virus having drug resistance has been recently a focus in drug study field.
At present, there are only three public listed non-nucleoside reverse transcriptase inhibitors (Nevirapine, Delavirdine, Efavirenz). These drugs have advantages of structural diversity, high efficiency and low toxicity, clear target and action mechanism as well as non-competitive inhibitors, and occupy important places in anti HIV combination therapy (HAART). However, their main problem is to cause drug resistance easily. In order to overcome the disadvantages of the existing drugs, it is needed to seek a new generation of non-nucleoside reverse transcriptase inhibitors drugs which can effectively inhibit the replication of wild type and multiple drug resistance HIV virus strains.